Comprehensive molecular portrait using next generation sequencing of resected intestinal-type gastric cancer patients dichotomized according to prognosis
Bria, Emilio (Azienda Ospedaliera Universitaria Integrata (Verona, Itàlia))
Pilotto, Sara (Azienda Ospedaliera Universitaria Integrata (Verona, Itàlia))
Simbolo, M. (Università di Verona)
Fassan, M. (Università di Verona)
De Manzoni, G.. (Università di Verona)
Carbognin, L. (Azienda Ospedaliera Universitaria Integrata (Verona, Itàlia))
Sperduti, Isabella (Istituto Regina Elena (Roma, Itàlia))
Brunelli, M. (Università di Verona)
Cataldo, I. (Università di Verona)
Tomezzoli, A. (Università di Verona)
Mafficini, A. (Università di Verona)
Turri, G. (Università di Verona)
Karachaliou, Niki (Pangaea Biotech (Barcelona, Catalunya))
Rosell, R. (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Tortora, G. (Azienda Ospedaliera Universitaria Integrata (Verona, Itàlia))
Scarpa, A. (Università di Verona)
Data: |
2016 |
Resum: |
In this study, we evaluated whether the presence of genetic alterations detected by next generation sequencing may define outcome in a prognostically-selected and histology-restricted population of resected gastric cancer (RGC). Intestinal type RGC samples from 34 patients, including 21 best and 13 worst prognostic performers, were studied. Mutations in 50 cancer-associated genes were evaluated. A significant difference between good and poor prognosis was found according to clinico-pathologic factors. The most commonly mutated genes in the whole population were PIK3CA (29. 4%), KRAS (26. 5%), TP53 (26. 5%) MET (8. 8%), SMAD4 (8. 8%) and STK11 (8. 8%). Multiple gene mutations were found in 14/21 (67%) patients with good prognosis, and 3/13 (23%) in the poor prognosis group. A single gene alteration was found in 5/21 (24%) good and 6/13 (46%) poor prognosis patients. No mutation was found in 2/21 (9. 5%) and 4/13 (31%) of these groups, respectively. In the overall series, ß-catenin expression was the highest (82. 4%), followed by E-Cadherin (76. 5%) and FHIT (52. 9%). The good prognosis group was characterized by a high mutation rate and microsatellite instability. Our proof-of-principle study demonstrates the feasibility of a molecular profiling approach with the aim to identify potentially druggable pathways and drive the development of customized therapies for RGC. |
Nota: |
Altres ajuts: AIRC/MFAG14282 |
Nota: |
Altres ajuts: AIRC/IG11930 |
Nota: |
Altres ajuts: AIRC/5X100012182 |
Nota: |
Altres ajuts: AIRC/12214 |
Nota: |
Altres ajuts: MIUR/PRIN-2009X23L78 |
Nota: |
Altres ajuts: FIRBRBAP10AHJB |
Drets: |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Llengua: |
Anglès |
Document: |
Article ; recerca ; Versió publicada |
Matèria: |
Estòmac ;
Càncer ;
Resected gastric cancer |
Publicat a: |
Scientific reports, Vol. 6 (Marz 2016) , ISSN 2045-2322 |
DOI: 10.1038/srep22982
PMID: 26961069
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Registre creat el 2017-05-22, darrera modificació el 2024-09-05